Mechanism of action of the nitrosoureas--IV. Synthesis of the 2-haloethylnitrosourea-induced DNA cross-link 1-(3-cytosinyl),2-(1-guanyl)ethane.
The 2-haloethylnitrosoureas have been shown to form the cross-linked structure 1-(3-cytosinyl),2-(1-guanyl)ethane in DNA. This cross-link has now been synthesized by the reaction of O6-(2-fluoroethyl)guanosine with deoxycytidine in dimethyl sulfoxide followed by removal of the sugars by acid hydrolysis. This synthetic route supports the mechanism for cross-link formation in DNA that involves an initial attack on the O6-position of guanine, followed by a rearrangement and subsequent reaction with cytosine. It also provides a practical route to the synthesis of 1-(3-cytosinyl),2-(1-guanyl)ethane for studies involving formation of this cross-link in DNA.
MacFarland
J G
JG
Department of Pharmacology, University of Massachusetts Medical School, Worcester 01655.
Kirk
M C
MC
Ludlum
D B
DB
D000970:Antineoplastic Agents; D055598:Chemical Phenomena; D002621:Chemistry; D003432:Cross-Linking Reagents; D004247:DNA / Q000187:drug effects*; D003841:Deoxycytidine; D015226:Dinucleoside Phosphates / Q000138:chemical synthesis*; D006151:Guanosine / Q000031:analogs & derivatives; D013058:Mass Spectrometry; D009607:Nitrosourea Compounds / Q000494:pharmacology*; D013056:Spectrophotometry, Ultraviolet
D000970:Antineoplastic Agents; D003432:Cross-Linking Reagents; D015226:Dinucleoside Phosphates; D009607:Nitrosourea Compounds; D003841:Deoxycytidine; D006151:Guanosine; C062310:1-(3-cytosinyl)-2-(1-guanyl)ethane; C018296:fluoroethylguanosine; D004247:DNA